清热活血中药联用对急性脑缺血再灌注大鼠mTOR-ERRα-GLS信号通路的调节作用  

The regulation of the combination use of Kudiezi injection and Xueshuantong injection on middle cerebral artery occlusion rats viamTOR-ERRα-GLS signaling pathway

作　　者：张鹤 刘雪梅[2] 曾子修 刘晓汉[3] 张昕洋 田杨[3] 徐榛敏 张允岭 ZHANG He;LIU Xuemei;ZENG Zixiu;LIU Xiaohan;ZHANG Xinyang;TIAN Yang;XU Zhenmin;ZHANG Yunling(Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]中国中医科学院广安门医院针灸科,北京100053 [2]北京中医药大学东方医院实验中心 [3]北京中医药大学 [4]中国中医科学院西苑医院

出　　处：《环球中医药》2020年第6期947-952,共6页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(81774250);国家国际科技合作专项(2015DFA31130);国家重点基础研究发展计划(973计划)(2012CB518406);中医药传承与创新“百千万”人才工程(岐黄工程)——国家中医药领军人才支持计划(国中医药人教函〔2018〕12号)。

摘　　要：目的从mTOR-ERRα-GLS信号通路的角度探寻清热活血中药联用治疗脑梗死急性期的协同增效机制。方法采用线栓法制备左侧大脑中动脉阻塞脑梗死模型。将95只SD大鼠随机分为假手术组(Sham)、模型组(缺血1.5小时再灌注72小时,Model,3.6 mL/kg生理盐水)、清热组(KDZ,3.6 mL/kg苦碟子注射液)、活血组(XST,40 mg/kg注射用血栓通)、清热活血组(KDZ+XST,1.8 mL/kg苦碟子注射液+80 mg/kg注射用血栓通)。采用Garcia JH评分判定大鼠神经功能缺损程度,TTC染色法检测脑梗死体积,干湿重法检测大鼠脑含水量,Western blot法检测缺血侧皮层mTOR、ERRα、GLS蛋白的表达。结果(1)与模型组相比,三个中药组大鼠的神经功能缺损均有改善(P<0.05),脑梗死体积及脑含水量均显著性降低(P<0.05或P<0.01);清热活血组大鼠脑梗死体积较清热组和活血组有所降低(P<0.05),其余组间无明显差异。(2)与假手术组相比,模型组缺血侧皮层mTOR、ERRα、GLS蛋白表达均显著降低(P<0.01);与模型组相比,清热组、活血组缺血侧皮层ERRα,GLS蛋白表达显著增加(P<0.05或P<0.01),清热活血组缺血侧皮层mTOR、ERRα、GLS蛋白表达显著增加(P<0.05或P<0.01);与清热组相比,活血组缺血侧皮层GLS蛋白表达显著增加(P<0.05),清热活血组缺血侧皮层ERRα、GLS蛋白表达显著增加(P<0.05)。结论清热活血中药联用治疗脑梗死急性期可起到协同增效的目的,其作用机制可能是通过调控mTOR-ERRα-GLS信号通路,与增加脑组织中能量代谢,改善脑组织能量代谢紊乱密切相关。Objective To investigate the synergetic effects and mechanism of the combination use of Kudiezi injection and Xueshuantong injection on middle cerebral artery occlusion rats(MCAO)via mTOR-ERRα-GLS signaling pathway.Methods The model was based on modified method of Zea Longa.Ninety-five male Sprague Dawley rats were randomly divided into Sham group,Model group(ischemia 1.5 h and reperfusion 72 h,3.6 mL/kg physiological saline),KDZ group(3.6 mL/kg,Kudiezi injection),XST group(40 mg/kg,Xueshuantong injection)and KDZ+XST group(1.8 mL/kg Kudiezi injection+80 mg/kg Xueshuantong injection).The degree of neurological deficiency was evaluated by Garcia JH score.The volume of cerebral infarction was measured by TTC staining.The water content of brain in rats was measured by dry and wet weight methods.The expression of mTOR-ERR alpha-GLS protein was detected by western blot.Results(1)Compared with Model group,all the three treatment groups could improve the degree of neurological deficiency(P<0.05),reduce the volume of cerebral infarction and the brain water content(P<0.05 or P<0.01),compared with KDZ group or XST group,the KDZ+XST group could reduce the volume of cerebral infarction(P<0.05).(2)Compared with Sham group,the expression of mTOR,ERR alpha,GLS protein in Model group significantly decreased(P<0.01);compared with Model group,KDZ group and XST group could increase the expression of ERR alpha,GLS protein(P<0.05 or P<0.01),KDZ+XST group could increase the expression of mTOR,ERR alpha,GLS protein(P<0.05 or P<0.01);compared with KDZ group,the XST group could increase the expression GLS protein(P<0.05),KDZ+XST group could increase the expression of ERR alpha,GLS protein(P<0.05).Conclusion The combination use of Kudiezi injection and Xueshuantong injection could play the synergetic effects by regulating the expression of mTOR-ERRα-GLS signaling pathway,increasing energy metabolism and improving energy metabolism disorder in ischemic brain tissue.

关 键 词：脑梗死急性期 清热活血 苦碟子注射液 血栓通注射液 能量代谢 

分 类 号：R285.5[医药卫生—中药学]